Cabergoline, depicted below was approved for the treatment of Parkinson's disease but was subsequently withdrawn from the U.S. market because of undesirable agonization of the 5-HT2B receptor which leads to cardiac and non-cardiac fibrosis.

Typically, an ideal anti-Parkinson's agent will be a selective agonist for dopaminergic D2 receptor. In some cases, it may be preferable to have a compound have a higher affinity (and stronger agonist activity) for the dopaminergic D2 receptor over the D1 and D4 receptors. Weak to modest agonist activity on the 5-HT1B and/or 5-HT1D receptors may also be desirable. Studies have also shown that 5-HT2 receptor antagonism may also be desirable for the treatment of Parkinson's disease symptoms and/or for the reduction of undesirable side-effects, such as cardiac or non-cardiac fibrosis and psychiatric side-effects (Newman-Tancredi, J Pharmacology and Experimental Therapies (2002) 303(2):815-822). Depending on the treatment regimen, anti-Parkinson's agents may have a relatively short half-life (i.e., 1-5 hours) or a longer half-life (i.e., 20 hours or longer).
Accordingly, what is needed are cabergoline analogs which retain activity against central nervous disorders, such as, for example, Parkinson's disease and lack agonist activity, or very weak agonist activity, against the 5-HT2 receptors, including 5-HT2B and the 5-HT2C receptors.